Expression of genes encoding neuropeptides and enzymes in the brain, with emphasis on the hypothalamus, are being studied. We have isolated the rat vasopressin and oxytocin genes and have made constructs to evaluate structural functions of the genes through the use of transgenic mice. We have successfully obtained transgenic mice that express the rat oxytocin gene in the appropriate tissues. We are currently evaluating which parts of the transgene mediate the tissue specificity and physiological response. We hope to use this model to regulate or eliminate oxytocin expression to further assess the physiological role of oxytocin, important for parturition and lactation. We are continuing our attempts to express the rat vasopressin gene. We have identified a region of the basal midline midbrain of the rat that selectively regulates galanin (though not colocalized vasopressin) gene expression in the paraventricular and supraoptic nuclei of the hypothalamus. We are currently attempting to identify its neurotransmitter and the pathway used. We are mapping the distribution of neurons expressing nearly 20 genes in the human hypothalamus, thalamus, and hippocampus through the use of in situ hybridization which overcomes the limitations of detection with immunohistochemistry. These studies have demonstrated the estrogen-responsive cells in the human hypothalamus and the neurotransmitters they make.